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Biomedical subjects

F Bertoni

Publications and source records attributed to F Bertoni.

At least 91 records · Page 5Linked to original sources
PubMed1999

Myxoid synovial sarcoma: an underappreciated morphologic subset.

Focal myxoid change is a well-recognized feature of synovial sarcoma, but the presence of a predominantly myxoid stroma is rare. We describe seven cases of myxoid synovial sarcoma in which marked myxoid change initially obscured the diagnosis, leading to confusion (principally with malignant peripheral nerve sheath tumor). The median age (20 yr) and tumor location (four lower extremity, two upper extremity, and one head and neck region) were similar to those found in typical synovial sarcoma. Histologically, five cases were monophasic spindle cell lesions with a lacy appearance in areas with a prominent Alcian blue-positive myxoid stroma. Each case had foci with more typical features of synovial sarcoma, including a fascicular growth pattern with a variably collagenized stroma, stromal mast cells, a hemangiopericytoma-like vascular pattern, and calcification. Two cases showed small foci of glandular (biphasic) differentiation. Immunohistochemically, all of the seven cases were positive for epithelial membrane antigen, four of six were positive for pan-keratin, three of six were positive for S-100, two of four were positive for CD99, and six of six were negative for desmin. Clinical follow-up in six cases ranged from 8 to 48 months (median, 21 mo). Local recurrence developed in three patients at 9, 20, and 24 months, respectively. In one of these three patients, lung metastases developed at 13 months, and the patient died of disseminated disease at 23 months. In another of the three patients, lung metastases developed at 27 months. Three patients had no evidence of disease at 8, 15, and 15 months. Our data are too limited to indicate any clinical differences between myxoid synovial sarcoma and conventional synovial sarcoma Recognition of this rare histologic variant of synovial sarcoma is important because it can easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting in suboptimal therapy.

Adolescent↗
PubMed1999

CHK1 frameshift mutations in genetically unstable colorectal and endometrial cancers.

The protein encoded by the CHK1 gene plays an important role in the G2 checkpoint in mammalian cells. In its coding region it presents a sequence of nine consecutive adenines that are a potential site of mutations in tumors with microsatellite instability (MSI). We analyzed the presence of frameshift mutations in the CHK1 gene in human colon and endometrial cancer samples. In the same cancer samples genes known to be altered in these tumors (BAX, TGFBRII, and IGFIIR) were also analyzed. CHK1 frameshfit mutations were found in 1 out 10 colon cancers and 2 out of 7 endometrial cancers showing MSI. CHK1 alterations were associated with the presence of a high degree of MSI. No alterations were found in patients with tumors showing low frequency or lacking instability (microsatellite stable). The same was true for the other four genes analyzed. The insertion or deletion of one A in the poly A tract resulted in a truncated protein. Alterations of the CHK1 gene could represent an alternative way of cancer cells to escape from cell cycle control. Genes Chromosomes Cancer 26:176-180, 1999.

Biomarkers, Tumor↗
PubMed1999

Microsatellite instability and frameshift mutations in genes involved in cell cycle progression or apoptosis in ovarian cancer.

The loss of mismatch repair enzymes increases the mutation rate in microsatellites and coding regions of the genome and appears to be involved in drug resistance. The replication error (RER+) phenotype, associated with microsatellite instability, has been widely described for both familial and sporadic colon cancers and for gastric and endometrial tumors. For ovarian cancer, the incidence of RER+ cases among sporadic tumors is still uncertain. We analyzed epithelial ovarian tumors and ovarian carcinoma cell lines for microsatellite instability and for mutations in the coding regions of different genes, including the recently discovered human CHK-1 gene, which has an important role in controlling cell cycle progression and whose coding region contains a poly(A)9 tract. Microsatellite instability and frameshift mutations in coding regions of BAX, TGFbetaRII, IGFIIR, E2F-4, ICE, and CHK-1 genes were analyzed in ovarian cancer samples and cell lines by polymerase chain reaction (PCR). Approximately 26% of patients showed microsatellite instability in two or more loci. BAT-26 locus showed no alteration in primary tumors. We detected a BAX mutation in one tumor sample and a TGFbetaRII mutation in one cell line. Our findings confirm the presence of the RER+ phenotype in sporadic ovarian cancer. The low rate of mutation in genes previously reported to be altered in colon and gastric cancer suggests that other not yet identified genes might be altered and could play a role in tumor progression and response to treatment in RER+ ovarian tumors.

Adult↗
PubMed1998

A multifaceted study of human papillomavirus and prostate carcinoma.

BACKGROUND: The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS: The cases were comprised of 51 African-American (men at high risk for prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/ GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be 1 HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS: All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS: The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men.

Aged↗
PubMed1998

Prognostic relevance of C-myc gene expression in giant-cell tumor of bone.

Giant-cell tumor is a primary bone tumor, of uncertain origin, with the potential capacity to metastasize. To study the role of c-myc and c-fos oncogene overexpression in the tumorigenesis and metastatic spread of giant-cell tumors, 32 primary tumors were collected; of these, 19 remained disease-free and 13 metastasized to the lung. Samples of lung metastasis from these 13 patients were also available for study. The expression of c-myc and c-fos mRNA was studied by reverse transcription-polymerase chain reaction and by in situ hybridization. The expression of protein was studied by Western blot analysis and by immunohistochemistry. C-myc mRNA was overexpressed in 12 (38%) of the 32 primary tumors. Thirteen primary tumors metastasized to the lung; in nine (69%) of these, c-myc mRNA was overexpressed. The c-myc protein was overexpressed in seven (54%) of the 13 tumors that metastasized to the lung. C-fos was overexpressed in only one lung metastasis. A strong correlation between the overexpression of c-myc, and the occurrence of metastases was found: thus, c-myc seems a powerful prognosticator in giant-cell tumor. C-myc was overexpressed both in giant cells and in mononuclear cells, suggesting that both cell types are involved in the progression of this tumor.

Adolescent↗
PubMed1998

Bizarre parosteal osteochondromatous proliferation of bone.

A 47-year-old man presented with a painless mass of 7 months' duration, on the plantar aspect of the great toe of the right foot. Radiographs and CT images initially suggested an osteochondroma arising from the proximal phalanx of the great toe but there was no continuity between the medullary canal of the phalanx and the lesion. The mass was excised and a histological diagnosis of bizarre parosteal osteochondromatous proliferation of bone (Nora's disease) was made. The aggressive growth of this lesion may clinically suggest a neoplasm. Histological features, however, are those of a reactive lesion.

Bone Neoplasms↗
PubMed1998

Giant cell reparative granuloma of the phalanx of the hand with aggressive radiographic features.

This report describes a giant cell (reparative) granuloma in the proximal phalanx of the third finger of the right hand in a 52-year-old man. Radiographically it showed aggressive features with bony permeation, breaking of the cortex, and soft tissue extension. These features suggested a malignant lesion. Histology was characteristic of giant cell reparative granuloma. This lesion, along with aneurysmal bone cyst and giant cell tumor in the small bones of hand and foot, occasionally may show aggressive features mimicking a malignant lesion.

Biopsy↗
PubMed1998

Classification of bone tumors.

The classification of bone tumors relies on the cytologic features and products of tumor cells. This classification is reproducible and accepted by pathologists, oncologic surgeons and oncologists. Chondrogenic tumors are the second largest group of bone tumors. Their histologic pattern suggests a relationship to hyaline cartilage. Exostoses, or osteochondromas, represent about 1/3 of chondrogenic lesions. Chondromas are hyaline cartilage tumors which can be found centrally or subperiosteally; they may contain some calcifications and/or ossifications. Chondroblastomas are tumors whose cells produce, at least focally, a matrix similar to hyaline cartilage. Histology of chondromyxoid fibromas shows large or small areas where proliferating cells produce a matrix resembling the hyaline cartilage. Chondosarcomas are tumors whose malignant cells produce a cartilaginous matrix. Most of them occur in previously normal bones; they are classified as conventional or primary chondrosarcomas. Secondary chondrosarcomas result from the malignant transformation of a benign cartilaginous lesion less commonly enchondromas and most commonly osteocartilaginous exostoses, or osteochondromas. Less common variants include dedifferentiated, mesenchymal and clear cell chondrosarcomas. Osteogenic tumors are the third largest group of bone tumors, with osteosarcomas being the most frequent type. The most important criterion for a tumor to be considered an osteosarcoma is that the malignant tumor cells must produce a recognizable osteoid matrix, at least focally. Osteosarcomas are divided into three groups: osteoblastic, chondroblastic and fibroblastic, according to the dominant histologic feature. Osteosarcomas can be multifocal, synchronous or metachronous; they are also classified by the histologic grade of malignancy. Pathologically low grade lesions, which are clinically indolent, are generally known as low grade central and parosteal osteosarcomas.

Bone Neoplasms↗
PubMed1998

Treatment and prognosis in a series of primary extranodal lymphomas of the ocular adnexa.

BACKGROUND: The aim of this study was to assess clinicopathological characteristics and outcome in a series of primary ocular adnexal lymphomas (POALs). PATIENTS AND METHODS: Nineteen patients with localised (stage IE) POAL were followed for a median of 96 months (24-156). The diagnosis was based on surgical biopsies followed by immunohistochemistry in 16 cases or fine-needle aspiration followed by immunocytophenotypic analysis in three cases. Twelve patients were treated with local radiotherapy (RT), five with chemotherapy (CT), and two refused further therapy after apparently radical tumour removal achieved by the diagnostic excisional biopsy. RESULTS: The histological and immunological pattern was consistent with a diagnosis of MALT-type lymphoma (11 cases), follicular center non-Hodgkin's lymphoma (three cases). a large-cell variant of Burkitt's lymphoma (one case), and large-cell transformed MALT lymphoma (one case). Low-grade lymphoma was diagnosed in the three cases which underwent fine-needle aspiration biopsy. All of the patients achieved and maintained complete remission except for those treated with surgical excision alone (two MALT conjunctival lymphoma cases): one of these relapsed locally, the other experienced the systemic spread of a transformed diffuse large-cell lymphoma and died 72 months after diagnosis. The side effects consisted of two cases of RT-related cataract after 52 and 72 months. CONCLUSIONS: Regardless of histology, prognosis was excellent when surgery plus RT was adopted, and CT seems to be a valid alternative to RT. Surgery alone may be sub-optimal.

Adult↗
PubMed1998

Management of rare forms of lymphoma.

The recent Revised European-American Classification of Lymphoma (REAL) classification system has been shown to allow easy, accurate, and reproducible identification of several clinically distinctive lymphoma subtypes. Many of these well-recognized lymphoma entities are relatively rare, as shown by a recent large survey of more than 1400 non-Hodgkin's lymphoma (NHL) cases from eight different countries. The purpose of this article is to summarize the present information known about these less common entities. Particular attention will be paid to the management problems of the following subtypes: the marginal-zone B-cell lymphomas of nodal type (or monocytoid lymphoma, comprising 1.8% of total cases in the above-mentioned series), the extranodal marginal-zone B-cell lymphomas (or mucosa-associated lymphoma tissue [MALT] lymphomas, representing 7.6% of the cases), the splenic marginal-zone B-cell lymphomas (< 1% of cases), the mantle cell lymphomas (6% of cases), and the primary mediastinal large B-cell lymphomas (2.4% of cases). Also, the main non-cutaneous peripheral T-cell lymphoma types, which including the natural killer (NK) disorders comprise less than 12% of all lymphoma cases, are discussed.

Humans↗
PubMed1998

Long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a in polycythaemia vera.

We report on long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a (rIFN-alpha) in a series of 38 patients with polycythaemia vera (PV). In all patients haematocrit was first brought into the normal range by venesection; rIFN-alpha was then begun at a starting weekly dose of 9,000,000 IU. Complete response (CR) was defined as persistence of normal haematocrit without venesection and partial response (PR) as >50% reduction of phlebotomy requirement. Eleven patients (28.9%) achieved CR and 8 (21.0%) PR. Median duration of treatment for all responsive patients was 40 months; 12 patients are still responsive and under treatment after 13, 15, 25, 35, 40, 41, 43, 49, 50, 51, 52 and 52 months of therapy with rIFN-alpha. In responsive patients, rIFN-alpha also normalized leucocyte counts, platelet counts and spleen enlargement; rIFN-alpha also relieved generalized pruritus in all 10 patients displaying this symptom. Early toxicity (flu-like syndrome) was observed in 23.6% and late toxicity (severe weakness) in 13.1% of patients, requiring rIFN-alpha treatment suspension in all cases. Progression to leukaemia was observed in none of the 10 patients treated only with rIFN-alpha and in one of the 12 who received alkylating agents before enrolment in this study. According to these data, rIFN-alpha seems to be an effective and safe treatment option for PV.

Adult↗
PubMed1998

Osteosarcoma of the extremities with synchronous lung metastases: long-term results in 44 patients treated with neoadjuvant chemotherapy.

Between September 1986 and September 1991, 44 patients with lung metastases originating from an osteosarcoma of an extremity were treated with: primary chemotherapy, simultaneous resection of primary and metastatic lesions (when feasible), and then further chemotherapy. After primary chemotherapy, lung metastases disappeared in 5 patients, whereas in 11 patients they remained surgically unresectable. All 16 patients received local treatment of the primary tumor only. In the remaining 28 patients simultaneous surgical treatment of the primary and the metastatic tumor was performed. The removal of metastatic lesions was complete in 25 and incomplete in 3 patients. With a median follow-up of 8 years (5.5-10.8) all 14 patients who never achieved a tumor-free status died. Of the 30 patients who achieved remission 5 (17%) remained continuously free of disease and 25 developed new metastases, associated with local recurrence in 4 cases. The 5-year overall survival for all 44 patients of the study was 14%, and the 5-year disease-free survival for the 30 patients who reached remission was 17%. These results are significantly worse than those achieved with the same chemotherapy protocol in 144 contemporary patients with localized disease at presentation (73% disease-free and 79% overall survival). We conclude that, despite aggressive chemotherapy which is successful in patients with localized disease, the prognosis remains very poor for patients with osteosarcoma of the extremities with lung metastases at presentation, and justifies the use of novel therapies.

Adolescent↗
PubMed1998

Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin.

PURPOSE: In osteosarcoma of the extremity, a strong correlation between chemotherapy-induced necrosis and prognosis has been reported. The aim of this study was to investigate the possible factors that influence histologic response to primary chemotherapy. PATIENTS AND METHODS: In 272 patients with high-grade osteosarcoma of the extremity preoperatively treated with high-dose methotrexate (HDMTX), cisplatin (CDP), and doxorubicin (ADM), the histologic response to chemotherapy was evaluated and graded as complete (no viable tumor cells) or incomplete (persistence of viable tumor cells). Several factors, such as metastatic disease to the lung at diagnosis, sex, age, site and tumor volume, histologic subtype, serum alkaline phosphatase, lactate dehydrogenase (LDH), and methotrexate (MTX) pharmacokinetics were investigated to test their predictive significance on histologic response. RESULTS: Fifty-one patients with localized disease (20.6%) and none of the 25 patients with metastatic disease at presentation had a complete histologic response (P = .006). After multivariate analysis, performed on patients with localized disease only, MTX serum peak (> or = 700 micromol/L) and histologic subtype were proven to be significant predictive factors of histologic response. A complete response was seen in 28.8% of patients with 700 micromol/L or greater MTX serum levels and in 9.9% of those patients with lower levels (P = .001). The chondroblastic subtype was less responsive (6.1% of complete response), compared with the osteoblastic (16.3%), fibroblastic (33.3%), and telangiectatic (42.3%). CONCLUSION: Patients with metastatic osteosarcoma and localized chondroblastic osteosarcoma have a reduced chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum peak significantly influences tumor necrosis. A dose adaptation of MTX is recommended to obtain a serum peak of 700 micromol/L or greater when MTX is infused in 6 hours.

Adolescent↗
PubMed1998

Predictive factors for local recurrence in osteosarcoma: 540 patients with extremity tumors followed for minimum 2.5 years after neoadjuvant chemotherapy.

We investigated predictive factors for local recurrence in 540 patients with non-metastatic osteosarcoma of the extremity treated with surgery and neoadjuvant chemotherapy, between March 1983 and October 1994. The median follow-up was 7.5 (2.5-15) years. Local recurrences developed in 31 (6%) patients after a median time of 2 (0.5-7) years. Local recurrence did not correlate with patients' age and sex, histologic subtype, site and tumor volume, presence of pathologic fracture, chemotherapy regimen and type of surgery. Local recurrence-free survival (LRFS) correlated with the quality of surgical margins and response to chemotherapy: the 7-year LRFS was 97% after adequate surgical margins and 71% after inadequate surgical margins (p < 0.0001), and was 95% in good responders and 90% in poor responders (p = 0.001). Only 1 of 31 patients with local recurrence was free of disease 15 months after the last treatment, 3 were alive with uncontrolled disease and 27 died. This post-relapse outcome is significantly worse than in patients who relapsed with metastases only (25% free of disease, 0.5-9 years after the last treatment). We conclude that, in osteosarcoma of the extremity, limb-salvage procedures should be planned only when the preoperative staging indicates that it is possible to achieve adequate surgical margins. If the pathologic examination of the surgical specimen shows inadequate surgical margins, an immediate amputation should be considered, especially if the histologic response to preoperative chemotherapy was poor.

Adolescent↗
PubMed1998

Osteosarcoma of the bones of the foot--an easily misdiagnosed malignant tumor.

OBJECTIVE: To evaluate the frequency of osteosarcoma involving the foot and determine the clinical outcome of affected patients. MATERIAL AND METHODS: We retrospectively reviewed the cases of osteosarcoma encountered between 1911 and 1992 at the Rizzoli Orthopedic Institute. In particular, we analyzed whether common clinical, radiographic, or histologic features could lead to a correct diagnosis of osteosarcoma of the foot. RESULTS: The bones of the foot were the primary site of osteosarcomas in 12 cases--0.6% of the entire series of such tumors at our institution during the study period. The mean age of the patients was 33 years. Initial symptoms were usually pain and swelling. Late diagnosis was common; the mean time interval between the first symptoms and diagnosis was 28 months. Misdiagnoses occurred in 6 of the 12 cases (50%): osteoblastoma, chondroblastoma, chondrosarcoma, osteoid osteoma, desmoid fibroma, and osteomyelitis were, respectively, the initial diagnoses. Histologically, 5 of the 12 tumors (42%) were low-grade lesions. Four of the seven patients with a high-grade tumor died of metastatic disease after a mean survival of 50 months. Eight patients are alive with no evidence of disease after a mean follow-up of 162 months. CONCLUSION: When a painful swelling in a bone of the foot is observed, even if numerous benign conditions (such as fractures, infections, or benign bone tumors) are far more likely to occur, osteosarcoma must be ruled out to avoid delays in the treatment. Osteosarcomas of the foot may easily be misdiagnosed, especially because they almost always occur in adults, in contrast to osteosarcomas in general. High-grade tumors of the foot are as aggressive as other osteosarcomas and should be managed accordingly--with use of a safe-margins surgical procedure and chemotherapy.

Adolescent↗
PubMed1998

Neoadjuvant chemotherapy for high grade malignant fibrous histiocytoma of bone.

Between March 1983 and December 1994, 65 patients with malignant fibrous histiocytoma of bone in the extremities were treated with neoadjuvant chemotherapy administered according to four different regimens. A limb salvage was done in 58 patients (89%) and amputation in seven. The histologic response to preoperative chemotherapy was good (90% or more tumor necrosis) in 16 patients (25%) and poor in 49 (75%). At a median followup of 7 years (range, 2-13 years), 40 patients (69%) remained continuously free of disease and 20 patients experienced relapse (18 with metastases and two with local recurrences followed by metastases). The rate of disease free survival was significantly higher for patients who had a good response than for those who had a poor response (94% versus 61%), although no significant differences in histologic response and disease free survival were seen with the four different regimens. These results show that a high percentage of patients with malignant fibrous histiocytoma of the extremities can be cured with neoadjuvant chemotherapy and that for most of them it is possible to avoid amputation.

Adolescent↗